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KMID : 1034820210170040417
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Molecular & Cellular Toxicology
2021 Volume.17 No. 4 p.417 ~ p.428
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Subcutaneous toxicity of melittin-dKLA in ICR mice
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Sung Ji-Ham
Kim Yu-Ra
Yu Pei Fu
Kim Youn-Sub
Han Ik-Hwan
Bae Hyun-Su
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Abstract
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Background: Melittin, a major component of honeybee venom, is known to possess anti-allergic, anti-inflammatory, anti-arthritis, and anti-cancer. Despite its great promise as an agent for various diseases, the therapeutic applications of melittin have been severely limited by its nonspecific cytotoxicity and hemolytic activity.
Objective: We synthesized a hybrid peptide (melittin-dKLA), composed of melittin and the pro-apoptotic peptide (dKLA), and evaluated its potential toxicity in ICR mice following a single or repeated subcutaneous dose administration.
Results: Mice administered a single subcutaneous dose of melittin-dKLA showed no mortality or abnormal clinical signs in all animals. Similarly, mice administered a repeated subcutaneous dose of melittin-dKLA resulted in no deaths. Crust formation and induration were observed in the male and female mice in the 5 and 20 mg/kg, respectively. The hematological parameters and serum biochemical analysis did not show any changes by melittin-dKLA. In repeated subcutaneous dose study, the mice in the 20 mg/kg group showed a significant increase in the relative weight of the spleen compared to the control group. Although the difference was not statistically significant. Mice exhibited a common pattern of change.
Conclusion: Taken together, our results suggest that the toxicity of melittin-dKLA is higher than 20 mg/kg both as a single and a repeated subcutaneous administration in ICR mice. Thus, it is suggested that it will be an important data in the development of new drug for melittin-dKLA.
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KEYWORD
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Melittin-dKLA, Toxicity, Clinical sign, Hematology, Necropsy
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